Bisphosphonates are a class of drugs that have been used to treat bone-related diseases such as osteoporosis and other disorders such as associated loss of bone mass and strength. Bisphosphonates prevent the resorption of bone, thereby reducing occurrences of fractures in the spine or hip for example. Bisphosphonates are chemical analogues of pyrophosphate where the central P—O—P linkage has been replaced by the P—C—P bond. The diphosphonate group imparts sufficient affinity to the mineral phase of the bone so that administration of bisphosphonates results in a significant amount of deposition to the osseous tissue of the bone. Many bisphosphonate analogues are currently available for enhancing bone affinity and improving pharmacological activity. Besides their primary use in treating metabolic bone disease osteoporosis and Paget's disease, recent studies have shown that bisphosphonates can be used in tumours affecting the skeleton. It has been reported in New England Journal of Medicine, 335: 1785-1791 (1996) that treatment with bisphosphonates decreases the frequency of skeletal events for patients with multiple myeloma involving bone and breast cancer with osteolytic metastases. Furthermore, adjunctive treatment with bisphosphonates was shown to reduce the incidence and number of new bone and visceral metastases in women with high risk, breast cancer (New England Journal of Medicine, 339:398-400 (1998). However, there remains a need for new approaches that would improve drug efficacy and reduce the associated side effects.
Another example of a bone-related disease that is potentially a major orthopaedic problem is chronic osteomyelitis. Chronic osteomyelitis is caused by microorganisms infecting the bone and/or the bone marrow. The infection associated with osteomyelitis may be localized or it may spread through the periosteum, cortex, marrow, and cancellous tissue. Osteomyelitis can be treated medically or surgically and prolonged antibiotic therapy is normally used. However, there are serious side effects such as nephrotoxicity and hepatotoxicity associated with such treatment. Several delivery systems and materials have been used in order to provide efficient antibiotic delivery. Materials such as polymethylmathacrylate (PMMA) and other biodegradable materials such as hydroxyapatite, plaster of Paris and chitosan were used. A porous calcium hydroxyapatite ceramic (CHA) was used for sustained release of antibiotics by incorporating the antibiotics into the CHA blocks. (Shinto Y. et al, The Journal of Bone and Joint Surgery, 1992, 74-B: 600-604). PMMA loaded with a variety of antibiotics have been extensively studied (Jain A K et al, Skeletal Drug Delivery Systems, Int. J. Pharm, 2000, 206:1-12). A hydroxyapatite composite comprising plaster of Paris, chitosan and hydroxyapatite impregnated with an antibiotic was also studied (Krisanapiboon A. et al, Journal of Orthopaedic Surgery, 2006, 14(3): 315-318). However a major drawback encountered with the treatment of osteomyelitis is the risk of antibiotic resistance.
Thus, there is a need to provide a new way for targeting drug delivery to the bone. This need is solved by the complex and the respective uses of the complex including its pharmaceutical uses.